Subthalamic nucleus high-frequency stimulation generates a concomitant synaptic excitation-inhibition in substantia nigra pars reticulata
The Journal of Physiology. 2011-08-30; 589(17): 4189-4207
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1. J Physiol. 2011 Sep 1;589(17):4189-207. doi: 10.1113/jphysiol.2011.211367. Epub
2011 Jun 20.
Subthalamic nucleus high-frequency stimulation generates a concomitant synaptic
excitation-inhibition in substantia nigra pars reticulata.
Bosch C(1), Degos B, Deniau JM, Venance L.
(1)Dynamics and Pathophysiology of Neuronal Networks, INSERM U-1050, College de
France, 75005 Paris, France.
Deep brain stimulation is an efficient treatment for various neurological
pathologies and a promising tool for neuropsychiatric disorders. This is
particularly exemplified by high-frequency stimulation of the subthalamic nucleus
(STN-HFS), which has emerged as an efficient symptomatic treatment for
Parkinson’s disease. How STN-HFS works is still not fully elucidated. With dual
patch-clamp recordings in rat brain slices, we analysed the cellular responses of
STN stimulation on SNr neurons by simultaneously recording synaptic currents and
firing activity. We showed that STN-HFS caused an increase of the spontaneous
spiking activity in half of SNr neurons while the remaining ones displayed a
decrease. At the synaptic level, STN stimulation triggered inward current in 58%
of whole-cell recorded neurons and outward current in the remaining ones. Using a
pharmacological approach, we showed that STN-HFS-evoked responses were mediated
in all neurons by a balance between AMPA/NMDA receptors and GABA(A) receptors,
whose ratio promotes either a net excitation or a net inhibition. Interestingly,
we observed a higher excitation occurrence in 6-hydroxydopamine (6-OHDA)-treated
rats. In vivo injections of phaseolus revealed that GABAergic pallido-nigral
fibres travel through the STN whereas striato-nigral fibres travel below it.
Therefore, electrical stimulation of the STN does not only recruit glutamatergic
axons from the STN, but also GABAergic passing fibres probably from the globus
pallidus. For the first time, we showed that STN-HFS induces concomitant
excitatory-inhibitory synaptic currents in SNr neurons by recruitment of
efferences and passing fibres allowing a tight control on basal ganglia outflow.
PMID: 21690190 [Indexed for MEDLINE]